title: Survival and toxicity in patients with disseminated germ cell cancer aged 40 years and older.
abstract: BACKGROUND
  Germ-cell cancer (GCC) patients aged ≥40 years have a two-fold higher GCC-specific mortality. It has been hypothesized that reduced treatment intensity combined with increased treatment related toxicity could be the explanation. The objective was to analyze chemotherapy intensity, treatment related toxicity and survival in patients aged ≥40 years treated with standard chemotherapy for GCC compared with a younger control group that received similar treatment during the same period.
  
  
  METHODS
  From 1984 to 2011, 135 patients aged ≥40 years with disseminated GCC treated with bleomycin, etoposide and cisplatin (BEP). A control-group of 135 patients aged 18-35 years was randomly selected matched on year of BEP treatment. Cumulated doses of BEP as well as bone marrow toxicity, renal- and lung functions were recorded before, during and after termination of treatment. All patients were followed until death or October 1, 2011.
  
  
  RESULTS
  The cumulated doses of BEP were comparable between the two groups, however, more patients aged ≥40 years were reduced in bleomycin doses based on a decrease in carbon monoxide diffusion capacity corrected for haemoglobin (P = 0.03). No differences between the two groups were found regarding bone marrow toxicity or mean percentage changes in lung- or renal function. Patients aged ≥40 year had increased cancer specific mortality, HR = 4.8 (P = 0.005). In particular patients with disease progression after first line chemotherapy had increased mortality (P = 0.015). Moreover, the 5-year overall survival for patients aged ≥40 years was 82.5% compared to the expected 5-year survival of the background population of 96.3% (P <0.001).
  
  
  CONCLUSIONS
  Treatment related toxicity could not explain the increased cancer specific mortality in patients aged ≥40 years compared to a younger control-group, and while there were no differences in the administrated doses of cisplatin/etoposide, a decreased number of bleomycin doses were administered in the older patients. Apart from this, the inferior prognosis could be related to tumour biology, increased co-morbidity, or more severe toxicity in relation to second line treatment.
authors.affiliation: Copenhagen Prostate Cancer Center, Department of Urology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Frederik B
authors.initials: FB
authors.lastname: Thomsen
authors.forename: Mikkel
authors.initials: M
authors.lastname: Bandak
authors.forename: Maria F
authors.initials: MF
authors.lastname: Thomsen
authors.forename: Jakob
authors.initials: J
authors.lastname: Lauritsen
authors.forename: Ib J
authors.initials: IJ
authors.lastname: Christensen
authors.forename: Gedske
authors.initials: G
authors.lastname: Daugaard
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001761:Bleomycin / Q000008:administration & dosage / Q000009:adverse effects; D016022:Case-Control Studies; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy* / Q000473:pathology; D011379:Prognosis; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D001761:Bleomycin; D005047:Etoposide; D002945:Cisplatin
keywords: germ cell cancer; older patients; survival; treatment intensity; treatment toxicity